Epithelial Cell Mechanisms in Chronic Rhinosinusitis and Nasal Polyposis

Epithelial cells of the sinonasal mucosa form a dynamic barrier that regulates fluid secretion, mucociliary clearance and immune surveillance. In chronic rhinosinusitis and nasal polyposis, this barrier is compromised by disrupted tight junctions and reduced expression of adhesion molecules, leading to increased permeability and microbial translocation. Injured epithelium undergoes epithelial-mesenchymal transition (EMT) under the influence of cytokines such as transforming growth factor-β1 (TGF-β1), interferon-γ and interleukins, via SMAD and MAPK signalling, which promotes subepithelial fibrosis and polyp formation. Hypoxia and HIF-1α up-regulate mucin production, exacerbating mucus stasis. Altered proliferation of basal stem/progenitor cells further impairs repair and sustains aberrant remodelling. Engagement of innate receptors such as TLR4 triggers release of pro-inflammatory cytokines and matrix metalloproteinases, reinforcing tissue remodelling. Distinct endotypes characterised by Th2-dominant or neutrophil-dominant inflammation define the epithelial response and inform targeted therapeutic strategies aimed at restoring barrier integrity and inhibiting maladaptive remodelling.

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Epithelial Cell Mechanisms in Chronic Rhinosinusitis and Nasal Polyposis publication trend

The graph below shows the total number of articles in epithelial cell mechanisms in chronic rhinosinusitis and nasal polyposis across all publications each year (not limited to Nature Index journals).

Technical terms

Epithelial-mesenchymal transition (EMT): a process whereby epithelial cells lose polarity and intercellular adhesion, acquiring mesenchymal traits and migratory capacity.

Tight junction proteins: multiprotein complexes (e.g. ZO-1, occludin) that seal intercellular spaces and maintain epithelial barrier integrity.

Transforming Growth Factor-β1 (TGF-β1): a cytokine that initiates EMT and fibrotic responses via activation of SMAD transcription factors.

SMAD signalling pathway: intracellular mediators of TGF-β signals that regulate gene transcription to drive EMT and extracellular matrix deposition.

Mitogen-Activated Protein Kinases (MAPK): a family of kinases, including ERK and p38, that transmit extracellular signals to control proliferation, differentiation and EMT.

Mucin 5AC (MUC5AC): a gel-forming mucin produced by epithelial cells, whose overproduction contributes to mucus hypersecretion and stasis.

Toll-Like Receptor 4 (TLR4): an innate immune receptor recognising bacterial lipopolysaccharide and triggering inflammatory cytokine and metalloproteinase release.

References

1. The interplay of inflammation and remodeling in the pathogenesis of chronic rhinosinusitis: current understanding and future directions. Frontiers in Immunology (2023).
2. The Inhibition Effect and Mechanism of Staurosporine Isolated from Streptomyces sp. SNC087 Strain on Nasal Polyp. Marine Drugs (2024).
3. The IFN-γ–p38, ERK kinase axis exacerbates neutrophilic chronic rhinosinusitis by inducing the epithelial-to-mesenchymal transition. Mucosal Immunology (2019).
4. Lipopolysaccharide Induces Pro-Inflammatory Cytokines and MMP Production via TLR4 in Nasal Polyp-Derived Fibroblast and Organ Culture. PLOS ONE (2014).
5. Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro. Scientific Reports (2014).
6. Hypoxia-Mediated Mechanism of MUC5AC Production in Human Nasal Epithelia and Its Implication in Rhinosinusitis. PLOS ONE (2014).
7. Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review. International Journal of Molecular Sciences (2021).